Relapsing-remitting multiple sclerosis Nervous System Diseases Multiple sclerosis
Conditions
Interventions
Current interventions as of 07/10/2022:
The StarMS study will run in multiple hospitals throughout the UK. It will compare treatment with autologous haematopoietic stem cell transplantation (aHSCT) wi
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
16 Years to 55 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 07/10/2022: 1. Diagnosis of MS using the 2017 McDonald criteria 2. Age 16-55 years inclusive 3. EDSS 0-6.0 inclusive*a. If the EDSS score is 6.0 this must be due to confirmed relapse rather than progressive disease 4. Severe inflammatory disease defined as RRMS course with 1 or more protocol-defined relapses*b, or evidence of MRI disease activity*c in the last 12 months (at the time of screening) despite being on a DMT, or rapidly evolving severe MS*d in treatment naïve patients*e 5. Clinical stability for >30 days following last relapse at the time of screening 6. Participants who have been reviewed by the central neurology team and confirmed as eligible 7. Participants who, in the opinion of the local haematology lead or delegate, are fit enough to undergo treatment. 8. Able to undergo MRI examination *a. Patients with EDSS scores of 0-1.5 must also fulfil the following criteria: short illness duration ( 3 months before or after its onset, in the last 12 months despite being on a DMT* 5. Clinical stability for >30 days following last relapse at the time of screening 6. Participants who have been reviewed by the central neurology team and confirmed as eligible 7. Participants who, in the opinion of the local haematology lead or delegate, are fit enough to undergo treatment. 8. Able to undergo MRI examination *Patients with EDSS scores of 0-1.5 or those who failed only first-line treatments must also fulfil the following criteria: short illness duration (<5 years), active disease clinically and radiologically (i.e. at least 2 relapses in the last 12 months and evidence of multiple Gad enhancing MRI lesion), high brain lesion load and brain or spinal cord atrophy Previous inclusion criteria: 1. Diagnosis of MS using the 2017 McDonald criteria 2. Age 16-55 years inclusive 3. EDSS 0-6.0 inclusive*. If the EDSS
Exclusion criteria
Exclusion criteria: Current key exclusion criteria as of 06/05/2026: 1. Diagnosis of primary or secondary progressive MS 2. Disease duration of > 10 years from symptom onset (note: symptoms must be clearly attributable to MS) 3. Previous use of alemtuzumab, ocrelizumab, ofatumumab or cladribine 4. Previous HSCT for any reason, or any previous experimental or commercial stem cell therapy 5. JCV antibody Index of > 1.5 in patients previously treated with natalizumab (unless they are CSF JCV PCR negative) 6. Prior diagnosis of Hepatitis B, Hepatitis C or HIV infection or current TB infection 7. Pregnant or breastfeeding females 8. Unwilling to use adequate contraception during the trial. Female participants of child-bearing potential must use adequate contraception for the duration of the trial (24 months), and for 12 months after discontinuation of cyclophosphamide, or 4 months after the last dose of alemtuzumab, or 6 months after the last dose of cladribine, or 3 months after the last dose of ocrelizumab and ofatumumab. Male participants with female partners of child-bearing potential must use adequate contraception if they are randomised to the aHSCT arm or cladribine during treatment and for at least six months following discontinuation (i.e. the last dose) of cyclophosphamide or cladribine 9. Unable to comply with treatment protocol 10. Contraindication to the use of cyclophosphamide, G-CSF (filgrastim or lenograstim) or rabbit ATG 11. Participants with significant medical co-morbidity that precludes aHSCT as assessed by the local haematology team 12. Significant language barriers, which are likely to affect the participant’s understanding of the study, or the ability to complete outcome questionnaires 13. Concurrent participation in another interventional clinical trial 14. AST or ALT >2.5 x upper limit of normal (ULN), bilirubin > 1.5 x ULN or direct bilirubin >ULN for participants with total bilirubin levels >1.5 x ULN 15. Current diagnosis of a clinically defined bleeding disorder (patients with platelet counts of 100x109/l or above up to normal range are not excluded, as per section 18d. Persistently abnormal coagulation tests should be addressed to determine whether they constitute a defined bleeding disorder) 16. Diagnosis of a clinically defined autoimmune disorder other than multiple sclerosis. (i.e. meeting full current international clinical and laboratory criteria for a specific autoimmune disorder) 17. Patients with a history of myocardial infarction, angina pectoris, stroke or arterial dissection 18. Participants who are not considered medically fit for aHSCT defined by any of the following. Note that these criteria are not automatic exclusion criteria but if any of these criteria are met, and in the opinion of the PI the participant is medically fit enough to undergo aHSCT, the case may be put forward to the central team for discussion about eligibility: 18.1. Renal: creatinine clearance < 40ml/min (measured or estimated) 18.2. Cardiac: clinical evidence of refractory congestive heart failure, left ventricular ejection fraction < 45% by cardiac echo; uncontrolled ventricular arrhythmia; pericardial effusion with haemodynamic consequences as evaluated by an experienced echocardiographer 18.3. Concurrent neoplasms or myelodysplasia 18.4. Bone marrow insufficiency defined as neutropenia with an absolute neutrophil count < 1x109/l, or thrombocytopenia with a platelet count < 100x109/l, or anaemia with a haemoglobin < 100g/l 18.5. Diagnosis of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients who have maintained NEDA status (defined as the absence of all three of the following: protocol-defined clinical relapses; 6 months confirmed EDSS progression of at least 1 point with an absence of relapse at the time of assessment; any evidence of MRI disease activity as defined by T1 Gd-enhanced lesion or new and/or enlarging T2 lesion after month 6) in the 2-year post-randomisation follow up period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current key secondary outcomes as of 06/05/2026: Safety assessed using: 1. Serious adverse event (SAE) rate within the 2-year follow up period 2. Mortality rate (grade 5 SAEs) within the 2-year follow up period 3. Combined grade 4 and 5 SAE rates within the 2-year follow up period 4. Total number of adverse events (AEs) experienced in the 100 days post-randomisation 5. Total number of AEs within the 2-year follow up period 6. Long-term safety events, including rates of significant infections, endocrine and reproductive dysfunction, secondary autoimmune diseases, incidence of late cardiovascular events, neoplasia and any other significant organ dysfunction within the 2-year follow up period (ongoing data will be recorded for aHSCT participants via routing BSBMT/EBMT registry, however, follow-up and analysis will be subject to additional funding and support) Clinical outcomes assessed using: 1. Time to evidence of disease activity. Disease activity is defined as the presence of one of the following: protocol-defined clinical relapses; confirmed EDSS progression of at least 1 point sustained for 6 months with an absence of relapse at the time of assessment; evidence of MRI disease activity defined as T1 Gd-enhanced lesion or new and/or enlarging T2 lesion after the re-baseline MRI at 6 months post-randomisation 2. EDSS scores at 3, 6, 9, 12, 18 and 24 months post-randomisation 3. MSFC scores at 3, 6, 9, 12, 18 and 24 months post-randomisation 4. Low contrast visual acuity scores at 3, 6, 9, 12, 18 and 24 months post-randomisation 5. Symbol digit modalities test (SDMT) scores at 3, 6, 9, 12, 18 and 24 months post-randomisation Quality of life/health economic measures assessed using: 1. EQ-5D-5L utility scores at 3, 6, 9, 12, 18 and 24 months post-randomisation 2. Eight RAND SF-36 dimension (physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general h | — |
Countries
England, Scotland, United Kingdom, Wales
Contacts
Public ContactRachel Glover
Outcome results
None listed